A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni.

The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen's virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-α. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ∆ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.

Cardiopulmonary Effects of Constant-Rate Infusion of Lidocaine for Anesthesia during Abdominal Surgery in Goats.

Lidocaine is commonly used in ruminants but has an anecdotal history of being toxic to goats. To evaluate lidocaine's effects on selected cardiopulmonary parameters. Isoflurane-anesthetized adult goats (n = 24) undergoing abdominal surgery received a loading dose of lidocaine (2.5 mg/kg) over 20 min followed by constant-rate infusion of lidocaine (100 µg/kg/min); control animals received saline instead of lidocaine. Data collected at predetermined time points during the 60-min surgery included heart rate, mean arterial blood pressure, pO2, and pCO2. According to Welch 2-sample t tests, cardiopulmonary variables did not differ between groups. For example, after administration of the loading dose, goats in the lidocaine group had a mean heart rate of 88 ± 28 bpm, mean arterial blood pressure of 70 ± 19 mm Hg, pCO2 of 65 ± 13 mm Hg, and pO2 of 212 ± 99 mm Hg; in the saline group, these values were 90 ± 16 bpm, 76 ± 12 mm Hg, 61 ± 9 mm Hg, and 209 ± 83 mm Hg, respectively. One goat in the saline group required an additional dose of butorphanol. Overall our findings indicate that, at the dose provided, intravenous lidocaine did not cause adverse cardiopulmonary effects in adult goats undergoing abdominal surgery. Adding lidocaine infusion during general anesthesia is an option for enhancing transoperative analgesia in goats.

Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours of inhalation anaesthesia in dorsally recumbent horses.

OBJECTIVE: The study aimed to investigate the effect of varying pulse lengths of inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on pulmonary gas exchange in anaesthetized horses. STUDY DESIGN: Experimental study. ANIMALS: Six Standardbred horses. METHODS: Horses received acepromazine, detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in dorsal recumbency and were breathing spontaneously. iNO was on average pulsed during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The pulse length that corresponded to the highest (peak) partial pressure of arterial oxygen (PaO(2) ) in the individual horses was determined and delivered for a further 1.5 hours. Data measured or calculated included arterial and mixed venous partial pressures of O(2) and CO(2) , heart rate, respiratory rate, expired minute ventilation, pulmonary and systemic arterial mean pressures, cardiac output and venous admixture. Data (mean ± SD) was analysed using anova with p < 0.05 considered significant. RESULTS: Although the pulse length of iNO that corresponded to peak PaO(2) varied between horses, administration of all pulse lengths of iNO increased PaO(2) compared to baseline. The shortest pulse lengths that resulted in the peak PaO(2) were 30 and 43% of the inspiration. Administration of iNO increased PaO(2) (12.6 ± 4.1 kPa [95 ± 31 mmHg] at baseline to a range of 23.0 ± 8.4 to 25.3 ± 9.0 kPa [173 to 190 mmHg]) and PaCO(2) (8.5 ± 1.2 kPa [64 ± 9 mmHg] to 9.8 ± 1.5 kPa [73 ± 11 mmHg]) and decreased venous admixture from 32 ± 6% to 25 ± 6%. The increase in PaO(2) and decrease in venous admixture was sustained for the entire 2.5 hours of iNO delivery. CONCLUSIONS: The improvement in arterial oxygenation during pulsed delivery of iNO was significant and sustained throughout 2.5 hours of anaesthesia. CLINICAL RELEVANCE: Pulsed iNO potentially could be used clinically to counteract hypoxemia in anaesthetized horses.

Physiologic responses and plasma endothelin-1 concentrations associated with abrupt cessation of nitric oxide inhalation in isoflurane-anesthetized horses.

OBJECTIVE: To assess physiologic responses and plasma endothelin (ET)-1 concentrations associated with abrupt cessation of nitric oxide (NO) inhalation in isoflurane-anesthetized horses. ANIMALS: 6 healthy adult Standardbreds. PROCEDURES: Horses were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. Nitric oxide was pulsed into the respiratory tract for 2.5 hours, and then administration was abruptly discontinued. Just prior to commencement and at cessation of NO administration, and at intervals during a 30-minute period following cessation of NO inhalation, several variables including PaO(2), mean pulmonary artery pressure, venous admixture or pulmonary shunt fraction (Qs/Qt), and plasma ET-1 concentration were recorded or calculated. RESULTS: After cessation of NO inhalation, PaO(2) decreased slowly but significantly (172.7 +/- 29.8 mm Hg to 84.6 +/- 10.9 mm Hg) and Qs/Qt increased slowly but significantly (25 +/- 2% to 40 +/- 3%) over a 30-minute period. Mean pulmonary artery pressure increased slightly (14.0 +/- 1.3 mm Hg to 16.8 +/- 1 mm Hg) over the same time period. No change in serum ET-1 concentration was detected, and other variables did not change or underwent minor changes. CONCLUSIONS AND CLINICAL RELEVANCE: The improvement in arterial oxygenation during pulsed inhalation of NO to healthy isoflurane-anesthetized horses decreased only gradually during a 30-minute period following cessation of NO inhalation, and serum ET-1 concentration was not affected. Because a rapid rebound response did not develop, inhalation of NO might be clinically useful in the treatment of hypoxemia in healthy isoflurane-anesthetized horses.

Effects of extradural morphine on end-tidal isoflurane concentration and physiological variables in pigs undergoing abdominal surgery: a clinical study.

OBJECTIVE: To evaluate the effects of preoperative extradural morphine on the end-tidal isoflurane (Fe'ISO) concentration and on physiological variables in pigs undergoing abdominal surgery. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: Fourteen healthy pigs (20 +/- 4 kg) undergoing intestinal cannulation. MATERIALS AND METHODS: Anaesthesia was induced with a combination of medetomidine (50 microg kg(-1)) and tiletamine-zolazepam (2.5 mg kg(-1)) injected intramuscularly, and was maintained with isoflurane in air and oxygen (FiO(2) = 50% O(2)). In the first group, morphine (0.1 mg kg(-1)) was administered extradurally before surgery. The second group received an equivalent volume of extradural saline as control. During the experiment, heart and respiratory rates, mean arterial blood pressure, tidal volume and minute ventilation were recorded every 10 minutes. The concentration of Fe'ISO was adjusted, according to the depth of anaesthesia, by an experienced animal nurse. Within treatment groups, time-related changes in Fe'ISO and physiological variables were analysed using a repeated measurement anova. Differences in data between treatment groups were analysed at specific time points using a Mann-Whitney U-test. Results are presented as mean +/- SD; p < 0.05 was considered as significant. RESULTS: After the onset of action of the morphine, the Fe'ISO required to maintain anaesthesia was significantly lower in the extradural morphine group compared with control. During the expected maximal effect of the drug, Fe'ISO was significantly lower in the morphine group (0.6 +/- 0.2%) than in the control group (0.9 +/- 0.2%). The decrease in Fe'ISO indicated that the onset of action of morphine was approximately 30 minutes after injection. No significant differences in other clinical variables were found between the groups. CONCLUSION: Pigs that received extradural morphine before abdominal surgery achieved surgical anaesthetic depth at a lower Fe'ISO concentration. CLINICAL RELEVANCE: Extradural morphine allows abdominal surgery to be performed at a lower Fe'ISO concentrations.